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INTRODUCTION: Nosocomial pneumonia is a common infection associated with high mortality in hospitalized patients. Nosocomial pneumonia, caused by gram-negative bacteria, often occurs in the elderly and patients with co-morbid diseases. METHODS: Original research using a prospective cross-sectional design was conducted on 281 patients in an intensive care unit setting with nosocomial pneumonia between July 2015 and July 2019. For each nosocomial pneumonia case, data regarding comorbidities, risk factors, patient characteristics, Charlson comorbidity index (CCI), Systemic Inflammatory Response Syndrome (SIRS), and quick Sepsis-Related Organ Failure Assessment (qSOFA) points and treatment outcomes were collected. Data were analyzed by SPSS 22.0. RESULTS: Nosocomial pneumonia due to gram-negative bacteria occurred in patients with neurological disorders (34.87%), heart diseases (16.37%), chronic renal failure (7.12%), and post-surgery (10.68%). Worse outcomes attributed to nosocomial pneumonia were high at 75.8%. Mechanical ventilation, change of antibiotics, and CCI ≥ 3 and qSOFA ≥ 2 were significantly negative prognostic factors (p < 0.05) on outcomes of nosocomial pneumonia. There was no difference in treatment effects between gender, age, time of onset pneumonia, SIRS score (p > 0.05). The pathogens were significant factors that influence treatment effects, but they weren't independent risk factors for poor outcomes (p = 0.823). CONCLUSIONS: Patients with nosocomial pneumonia hospitalized in intensive care units are usually associated with many underlying diseases, including neurological diseases. Mechanical ventilation, a change in antibiotics, CCI ≥ 3, and qSOFA ≥ 2 are also associated with a worse prognosis of nosocomial pneumonia. CCI and qSOFA might be used in predicting the outcome of nosocomial pneumonia.
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Early clinical results of chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) appear promising, but relapses associated with residual low-to-negative BCMA-expressing MM cells have been reported, necessitating identification of additional targets. The orphan G protein-coupled receptor, class C group 5 member D (GPRC5D), normally expressed only in the hair follicle, was previously identified as expressed by mRNA in marrow aspirates from patients with MM, but confirmation of protein expression remained elusive. Using quantitative immunofluorescence, we determined that GPRC5D protein is expressed on CD138+ MM cells from primary marrow samples with a distribution that was similar to, but independent of, BCMA. Panning a human B cell-derived phage display library identified seven GPRC5D-specific single-chain variable fragments (scFvs). Incorporation of these into multiple CAR formats yielded 42 different constructs, which were screened for antigen-specific and antigen-independent (tonic) signaling using a Nur77-based reporter system. Nur77 reporter screen results were confirmed in vivo using a marrow-tropic MM xenograft in mice. CAR T cells incorporating GPRC5D-targeted scFv clone 109 eradicated MM and enabled long-term survival, including in a BCMA antigen escape model. GPRC5D(109) is specific for GPRC5D and resulted in MM cell line and primary MM cytotoxicity, cytokine release, and in vivo activity comparable to anti-BCMA CAR T cells. Murine and cynomolgus cross-reactive CAR T cells did not cause alopecia or other signs of GPRC5D-mediated toxicity in these species. Thus, GPRC5D(109) CAR T cell therapy shows potential for the treatment of advanced MM irrespective of previous BCMA-targeted therapy.